Based on experimental and theoretical studies reported to date on RNase-S' it was postulated that the minimum structural information expressed in the N-terminal sequence of RNase-S is an alpha-helix on which the residues Phe and Met are specifically positioned for maximal apolar interactions with RNase (21-123). To test this postulate, a model dodecapeptide was previously designed and synthesized by solid phase method. Properties of this peptide in terms of its solution conformation and its affinity toward S-protein were characterized. Further, the ability of this peptide to help direct the regeneration of active RNase '21-124) tertiary structure, after the initial scrambling of the disulfide bonds, was determined. For crystallographic structural analysis, purified model sRNase-S' was successfully crystallized in the same space group as native complex. Efforts were made to crystallize synthetically derived native and model analogue peptides. At present, crystals of (Lla 13) sRNase (1-15) have been obtained. For a continuing study on RNase enzymatic mechanism, the characterization of the residual activity found for (4-F-His12, des 16-20) sRNase-S' and covalent (4-F-His12) sRNase-A is in progress.